Previous radiotherapy improves treatment responses and causes a trend toward longer time to progression among patients with immune checkpoint inhibitor-related adverse events.

BACKGROUND: Immune-related adverse events (irAEs) are frequently encountered by patients during immune checkpoint inhibitor (ICI) treatment and are associated with better treatment outcomes. The sequencing of radiotherapy (RT) and ICIs is widely used in current clinical practice, but its effect on survival has remained unclear. METHODS: In a real-world multicenter study including 521 patients who received ICI treatment for metastatic or locally advanced cancer, RT schedules and timing, irAEs, time to progression, overall survival, and treatment responses were retrospectively reviewed. RESULTS: Patients who received previous RT and developed irAE (RT +/AE +) had the best overall response rate (ORR 44.0%). The ORR was 40.1% in the RT -/AE + group, 26.7% in the RT -/AE - group and 18.3% in the RT + /AE - group (p < 0.001). There was a significantly longer time to progression (TTP) in the RT + /AE + group compared to the RT -/AE - and RT + /AE - groups (log rank p = 0.001 and p < 0.001, respectively), but the trend toward longer TTP in the RT + /AE + group did not reach statistical significance in pairwise comparison to that in the RT -/AE + group. Preceding RT timing and intent had no statistically significant effect on TTP. In a multivariate model, ECOG = 0 and occurrence of irAEs remained independent positive prognostic factors for TTP (HR 0.737; 95% CI 0.582-0.935; p = 0.012, and HR 0.620; 95% CI 0.499-0.769; p < 0.001, respectively). CONCLUSIONS: Better ORR and a trend toward longer TTP were demonstrated for patients with RT preceding ICI treatment and development of irAEs, which suggests that RT may boost the therapeutic effect of immunotherapy in patients with metastatic cancers.

Long-term outcome of biologically guided dose-escalated radiotherapy of localized prostate cancer.

BACKGROUND: Biologically created subvolumes enable non-uniform dose distributions in prostate cancer radiotherapy (RT) thus potentially improving therapeutic ratio and reducing toxicity. We present the long-term outcome of men receiving focal boosting of carbon-11 acetate (ACE) PET-CT metabolically active areas in prostate carcinoma. MATERIAL AND METHODS: Thirty men with hormone naïve localized prostate carcinoma underwent ACE PET/CT for RT planning. There were five low-, 17 intermediate-, and eight high-risk patients. Based on thresholding of the standardized uptake values (SUVs) metabolic target volumes (MTVs) corresponding to intraprostatic lesions (IPLs) were contoured. Two planning target volumes (PTVs) were applied i.e., PTVlow-risk for the whole prostate with 8-10 mm margin and PTVhigh-risk for the MTV. Pelvic nodes were not irradiated. Late toxicity of biologically guided RT was reviewed after a median of 63 months and outcome after a median follow-up of 124 months. RESULTS: Median doses to PTVlow-risk, PTVhigh-risk, prostate, and MTV were 72.9 Gy, 79.4 Gy, 76.6 Gy, and 80.4 Gy, respectively, in 38 fractions. The 10-year cancer-specific survival was 86% and the biochemical failure-free ratio 68%, respectively. The median biochemical progression-free survival (PFS) was 37, 108, and 119 months in the high, intermediate, and low-risk groups, respectively, the difference being significant between high and intermediate-risk groups (p = 0.02). One patient (3%) presented with locoregional and 5 (17%) with distant nodal metastases. Five patients (17%) had a biochemical relapse. A larger MTV was associated with shorter PFS (r = -0.41, p = 0.02), but had no influence on OS. No other statistically significant differences in the dose painting parameters were observed between recurrence-free and recurring patients. CONCLUSIONS: Biological guidance for dose-escalated prostate RT is feasible with ACE PET/CT. Since a larger MTV may be associated with a higher risk for progression, we encourage further study of dose-escalation to ACE-positive lesions considering the low toxicity of our protocol.

Geometrical uncertainty of heart position in deep-inspiration breath-hold radiotherapy of left-sided breast cancer patients.

BACKGROUND: This study aimed to determine the geometrical uncertainty of the position of the heart with daily cone beam computed tomography (CBCT) during deep-inspiration breath-hold (DIBH) treatment of the left breast. MATERIAL AND METHODS: A visually guided optical respiratory monitoring system was used in DIBH treatment of 15 breast cancer patients. Heart position was determined in relation to the planning target volume (PTV) in 225 fractions in which daily low-dose CBCT images were compared with planning CT images. In addition, the position of the left lung apex and diaphragm was measured to evaluate the success of the DIBH. RESULTS: The median shift of the heart was 1 mm to the left, 1 mm superiorly and 0 mm in the anterior-posterior (AP) direction during the treatment course when compared to the PTV position in planning CT. Based on these movements, an AP margin of 4 mm, a lateral (LR) margin of 3 mm, and a superior-inferior (SI) margin of 5 mm should be added to the heart contour to ensure avoiding the heart when planning treatment. The distance between the left lung apex and diaphragm, applied as a surrogate for lung volume, was 2mm (median) smaller during the CBCT acquisitions than during the planning CT acquisition. The correlation coefficient between the surrogate of lung volume and the distance between the heart and PTV was r = .46 in the AP, r = .72 in the LR and r = .79 in the SI directions. CONCLUSION: Residual variation was observed in the position of the heart in comparison to PTV, even with a visually guided DIBH technique. These geometrical uncertainties should be taken into account when planning radiotherapy treatment. The success of DIBH may make a major contribution to the variation of the heart position during treatment.

Hypofractionated stereotactic body radiotherapy for localized prostate cancer - first Nordic clinical experience.

BACKGROUND: The use of hypofractionated stereotactic body radiotherapy (SBRT) as primary treatment modality in clinically localized prostate cancer (PCa) is emerging, because the low α/ß-ratio favors the use of high dose per fraction in PCa. There is a need for more data about SBRT, especially in high-risk PCa patients. The purpose of this retrospective study was to evaluate the safety and the short-term efficacy of robotic SBRT in a clinical patient cohort with localized PCa including also high-risk patients (D'Amico risk stratification). MATERIALS AND METHODS: A total of 240 consecutive patients with clinically localized PCa were treated primarily with SBRT to total doses of 35 Gy or 36.25 Gy in 5 fractions using a robotic SBRT device (CyberKnife®). All risk groups (D'Amico risk stratification) were represented as follows: 48 (22%), 59 (27%) and 111 (51%) of the patients representing low-, intermediate- and high-risk group, respectively. Data on acute and intermediate-term toxicities and early PSA responses were analyzed. RESULTS: Neither acute grade 3 or higher GU nor rectal toxicity was observed. Regardless of the fact that 29 (13.3%) patients experienced intermediate-term toxicity requiring diagnostic interventions, the rates of intermediate-term grade 3 GU, rectal and infectious toxicity were low, 1.8%, 0.9% and 1.4%, respectively. A biochemical relapse was observed in ten (4.6%) patients. With the median follow-up time of 23 months the biochemical relapse-free survival (bRFS) rate was 100%, 96.6% and 92.8% in low-, intermediate- and high-risk group, respectively. CONCLUSIONS: The toxicity of robotic SBRT in a large clinical cohort of PCa patients was tolerable and the early PSA response was good in all risk groups. The hypofractionated SBRT offers a possibility to high dose per fraction and to provide the whole radiotherapy treatment within two to three weeks.

Open-Ended Coaxial Dielectric Probe Effective Penetration Depth Determination.

We have performed a series of experiments which demonstrate the effect of open-ended coaxial diameter on the depth of penetration. We used a two layer configuration of a liquid and movable cylindrical piece of either Teflon or acrylic. The technique accurately demonstrates the depth in a sample for which a given probe diameter provides a reasonable measure of the bulk dielectric properties for a heterogeneous volume. In addition we have developed a technique for determining the effective depth for a given probe diameter size. Using a set of simulations mimicking four 50 Ω coaxial cable diameters, we demonstrate that the penetration depth in both water and saline has a clear dependence on probe diameter but is remarkably uniform over frequency and with respect to the intervening liquid permittivity. Two different 50 Ω commercial probes were similarly tested and confirm these observations. This result has significant implications to a range of dielectric measurements, most notably in the area of tissue property studies.

Volumetric modulated arc therapy for synchronous bilateral whole breast irradiation - A case study.

PURPOSE: The treatment planning of bilateral breast irradiation (BBI) is a challenging task. The overlapping of tangential fields is usually unavoidable without compromising the target coverage. The purpose of this study was to investigate the technical feasibility and benefits of a single isocentre volumetric modulated arc therapy (VMAT) in BBI. METHODS AND MATERIALS: Two women with bilateral breast cancer were included in this case study. The first patient (Pat#1) underwent a bilateral breast-conserving surgery and sentinel lymph node biopsy. The second patient (Pat#2) underwent a bilateral ablation and axillary lymph node dissection. Planning target volumes (PTV) and organs at risk were delineated on CT images. VMAT plans were created with four (two for both sides, Pat#1) or two (one for each breast, Pat#2) separate VMAT fields. Subsequently, traditional tangential field plans were generated for each patient and the dosimetric parameters were compared. RESULTS: The treatment times of the patients with VMAT were less than 15 min with daily CBCT imaging. When compared to the standard tangential field technique, the VMAT plans improved the PTV dose coverage and dose homogeneity with improved sparing of lungs and heart. With traditional field arrangement, the overlapping of the tangential fields was inevitable without significantly compromising the target coverage, whereas with VMAT the hotspots were avoided. The patients were treated with the VMAT technique and no acute skin toxicity was observed with either of the patients. CONCLUSIONS: A single isocentre VMAT technique has been implemented clinically for BBI. With the VMAT techniques, the dose delivery was quick and the hotspots in the field overlapping areas were avoided. The PTV dose coverage was superior in VMAT plans when compared with conventional tangential technique plans.

Prognostic value of tumour blood flow, [¹8F]EF5 and [¹8F]FDG PET/CT imaging in patients with head and neck cancer treated with radiochemotherapy.

PURPOSE: In order to improve the treatment of squamous cell carcinoma of the head and neck, precise information on the treated tumour's biology is required and the prognostic importance of different biological parameters needs to be determined. The aim of our study was to determine the predictive value of pretreatment PET/CT imaging using [(18)F]FDG, a new hypoxia tracer [(18)F]EF5 and the perfusion tracer [(15)O]H2O in patients with squamous cell cancer of the head and neck treated with radiochemotherapy. METHODS: The study group comprised 22 patients with confirmed squamous cell carcinoma of the head and neck who underwent a PET/CT scan using the above tracers before any treatment. Patients were later treated with a combination of radiochemotherapy and surgery. Parametric blood flow was calculated from dynamic [(15)O]H2O PET images using a one-tissue compartment model. [(18)F]FDG images were analysed by calculating standardized uptake values (SUV) and metabolically active tumour volumes (MATV). [(18)F]EF5 images were analysed by calculating tumour-to-muscle uptake ratios (T/M ratio). A T/M ratio of 1.5 was considered a significant threshold and used to determine tumour hypoxic subvolumes (HS) and hypoxic fraction area. The findings were finally correlated with the pretreatment clinical findings (overall stage and TNM stage) as well as the outcome following radiochemotherapy in terms of local control and overall patient survival. RESULTS: Tumour stage and T-classification did not show any significant differences in comparison to the patients' metabolic and functional characteristics measured on PET. Using the Cox proportional hazards model, a shorter overall survival was associated with MATV (p = 0.008, HR = 1.108), maximum [(18)F]EF5 T/M ratio (p = 0.0145, HR = 4.084) and tumour HS (p = 0.0047, HR = 1.112). None of the PET parameters showed a significant effect on patient survival in the log-rank test, although [(18)F]EF5 maximum T/M ratio was the closest (p = 0.109). By contrast, tumour blood flow was not correlated with any of the clinical endpoints. There were no statistically significant correlations among [(18)F]FDG SUVmax, [(18)F]EF5 T/M ratio and blood flow. CONCLUSION: Our study in a limited number of patients confirmed the importance of MATV in the prognosis of locally advanced squamous cell carcinoma of the head and neck. It is of interest that high uptake of the hypoxia tracer [(18)F]EF5 showed a stronger correlation with a poor clinical outcome than [(18)F]FDG uptake. This confirms the importance of hypoxia in treatment outcome and suggests that [(18)F]EF5 may act as a surrogate marker of radioresistance.

50 Hz magnetic field influences caspase-3 activity and cell cycle distribution in ionizing radiation exposed SH-SY5Y neuroblastoma cells.

PURPOSE: Earlier evidence suggests that extremely low frequency magnetic fields (ELF MFs) can modify the effects of carcinogenic agents. However, the studies conducted so far with ionizing radiation as the co-exposure agent are sparse and have provided inconclusive results. We investigated whether 50 Hz MFs alone, or in combination with ionizing radiation alter cell biological variables relevant to cancer and the biological effects of ionizing radiation. MATERIALS AND METHODS: Human SH-SY5Y neuroblastoma cells were sham exposed or exposed to 100 or 500 µT MF for 24 h either before or after ionizing radiation exposure (0, 0.4 or 2 Gy). After the exposures, cells were assayed for viability, clonogenicity, reactive oxygen species, caspase-3 activity, and cell cycle distribution. Cell cycle distribution was assayed with propidium iodide staining followed by flow cytometry analysis and ROS levels were assayed together with cell viability by double staining with DeepRed and Sytox Blue followed by flow cytometry analysis. RESULTS: Increased caspase-3 activity was observed in cells exposed to 500 µT MF before or after ionizing radiation. Furthermore, exposure to the 500 µT MF after the ionizing radiation decreased the percentage of cells in S-phase. No changes in the ROS levels, clonogenicity, or viability of the cells were observed in the MF exposed groups compared to the corresponding sham exposed groups, and no MF effects were observed in cells exposed at 100 µT. CONCLUSIONS: Only the 500 µT magnetic flux density affected SH-SY5Y cells significantly. The effects were small but may nevertheless help to understand how MFs modify the effects of ionizing radiation. The increase in caspase-3 activity may not reflect effects on apoptosis, as no changes were observed in the subG1 phase of the cell cycle. In contrast to some earlier findings, 50 Hz MF exposure after ionizing radiation was not less effective than MF treatment given prior to ionizing radiation.

Dosimetric effect of respiratory motion on planned dose in whole-breast volumetric modulated arc therapy using moderate and ultra-hypofractionation.

BACKGROUND AND PURPOSE: The interplay effect of respiratory motion on the planned dose in free-breathing right-sided whole-breast irradiation (WBI) were studied by simulating hypofractionated VMAT treatment courses. MATERIALS AND METHODS: Ten patients with phase-triggered 4D-CT images were included in the study. VMAT plans targeting the right breast were created retrospectively with moderately hypofractionated (40.05 Gy in 15 fractions of 2.67 Gy) and ultra-hypofractionated (26 Gy 5 fractions of 5.2 Gy) schemes. 3D-CRT plans were generated as a reference. All plans were divided into respiratory phase-specific plans and calculated in the corresponding phase images. Fraction-specific dose was formed by deforming and summing the phase-specific doses in the planning image for each fraction. The fraction-specific dose distributions were deformed and superimposed onto the planning image, forming the course-specific respiratory motion perturbed dose distribution. Planned and respiratory motion perturbed doses were compared and changes due to respiratory motion and choice of fractionation were evaluated. RESULTS: The respiratory motion perturbed PTV coverage (V95%) decreased by 1.7% and the homogeneity index increased by 0.02 for VMAT techniques, compared to the planned values. Highest decrease in CTV coverage was 0.7%. The largest dose differences were located in the areas of steep dose gradients parallel to respiratory motion. The largest difference in DVH parameters between fractionation schemes was 0.4% of the prescribed dose. Clinically relevant changes to the doses of organs at risk were not observed. One patient was excluded from the analysis due to large respiratory amplitude. CONCLUSION: Respiratory motion of less than 5 mm in magnitude did not result in clinically significant changes in the planned free-breathing WBI dose. The 5 mm margins were sufficient to account for the respiratory motion in terms of CTV dose homogeneity and coverage for VMAT techniques. Steep dose gradients near the PTV edges might decrease the CTV coverage. No clinical significance was found due to the choice of fractionation.

Increased beam attenuation and surface dose by different couch inserts of treatment tables used in megavoltage radiotherapy.

The use of solid carbon fiber table materials in radiotherapy has become more common with the implementation of image-guided radiotherapy (IGRT), since the solid materials give less imaging artifacts than the so-called tennis racket couchtops. The downside of the solid carbon fiber couch inserts is that they increase the beam attenuation, resulting in increased surface doses and inaccuracies in determine the dose in the patient. The purpose of this study was to evaluate the interaction of 6 and 15 MV photons with eight different couch inserts. The presented results enable direct comparison of the attenuation properties of the studied couchtops. With a direct posterior beam the maximum attenuations reach 3.6% and 2.4% with 6 and 15 MV, respectively. The measured maximum attenuation by a couchtop with an oblique gantry angle was 10.8% and 7.4% at 6 and 15 MV energies, respectively. The skin-sparing effect was decreased substantially with every couchtop. The highest increases in surface doses were recorded to be four- and threefold, as compared to the direct posterior open field surface doses of 6 and 15 MV, respectively. In conclusion, the carbon fiber tabletops decrease the skin-sparing effect of megavoltage photon energies. The increased beam attenuation and skin doses should be taken into account in the process of treatment planning.

Is adaptive treatment planning for single-channel vaginal brachytherapy necessary?

PURPOSE: In vaginal cuff brachytherapy, only limited information is available about the need for individualized treatment planning or imaging. Treatment planning is still performed mostly with no contouring target volume or organs at risk and with standard plan approach. Dose prescription, fractionation, and treatment planning practices vary from site to site. Without imaging, dose must be prescribed in terms of fixed distances from a known reference, such as the applicator surface. Because of different anatomies of patients, this might lead to under-dosing of target and unnecessarily high-doses delivered to adjacent organs. Also, reliable recording of dose delivered is difficult. These various uncertainties related to standard planning and lack of imaging indicate a clear need for finding an optimal method of dose planning for vaginal cuff brachytherapy. MATERIAL AND METHODS: A study was conducted, in which 100 vaginal cuff brachytherapy patients' computed tomography (CT) images with applicator in situ were retrospectively analyzed to investigate target-area coverage and critical-organ doses. In addition, 28 patients' plans were re-planned with different planning approaches, to evaluate an optimal dose-planning strategy. From treatment plans, target coverage and organs-at-risk doses were assessed. RESULTS AND CONCLUSIONS: The analysis showed that, in order to cover distal part of the vaginal cuff, dose prescription should be a 10 mm from the tip of the applicator. Individualized image-based planning is recommended at least for first fraction. This would yield lower doses to the bladder. Rectum and sigmoid doses are not significantly affected by planning approach.

The robustness of VMAT radiotherapy for breast cancer with tissue deformations.

To investigate the near-surface doses and target coverage in modulated arc radiotherapy (RT) of the breast or chest wall in two treatment planning systems (TPS) in the presence of soft tissue deformations. This retrospective study consisted of 10 breast cancer patients with axillary lymph node inclusion. For each case, five RT plans were created: (1) tangential 3D conformal field-in-field (FinF) technique; (2) 200° to 240° arcs with optimization bolus (OB) in Eclipse (EB); (3) 243° to 250° arcs with an 8-mm OB in Monaco (MB); (4) 243° to 250° arcs with automatic skin flash tool (ASF) in Monaco TPS (MA); (5) 243° to 250° arcs with both ASF and OB in Monaco (MAB). Soft tissue deformation was simulated by editing CT-images with 4-, 8-, and 12-mm swelling and recalculating the dose. The increasing swelling from 0 to 12 mm caused the coverage (V95%) in clinical target volume to decrease from 96% ± 2% to 90% ± 6% for the FinF plans. For volumetric-modulated arc therapy (VMAT), the coverage decreased from 99% ± 1% to 92% ± 4% in the EB plans, and from 97% ± 1% to 68% ± 8%, 85% ± 6%, and 86% ± 5% for MA, MB, and MAB, respectively. The mean dose in the surface extending from 0 to 3 mm from the skin decreased on average 5%, 17%, 20%, 15%, and 8% in FinF, EB, MA, MB, and MAB, respectively. In the Monaco plans, the use of an OB(+ASF) provided better target coverage and lower dose maxima despite of tissue swelling than the ASF alone. With modulated arc therapy, we recommend the use of an OB instead of or in addition to the ASF. The use of 8 mm OB with VMAT plans is robust to account deformations extending outside up to 8mm. If soft tissue deformation is larger than 8 mm, the need for replanning should be evaluated.

Stereotactic body radiotherapy for localized prostate cancer - 5-year efficacy results.

BACKGROUND: The use of stereotactic body radiotherapy (SBRT) as the primary treatment modality in clinically localized prostate cancer (PCa) is emerging. The aim of the study was to analyze the long-term results of PCa patients treated with SBRT. METHODS: This non-selected, real-life patient cohort included 213 patients with localized PCa treated with a robotic SBRT device during 2012-2015. RESULTS: The median follow-up was 64 months (range, 10-85 months), and all risk-groups were represented as 47 (22.1%), 56 (26.3%) and 110 (51.6%) patients were classified into D'Amico risk stratification of low, intermediate and high-risk groups, respectively. Androgen deprivation therapy (ADT) was administered to 64.3% of the patients. At cut-off, the biochemical relapse-free survival (bRFS) was 100, 87.5 and 80.0% for patients at low, intermediate and high-risk (p = 0.004), and 92.5, 84.2 and 66.7% for patients with Gleason score ≤ 6, 7 and ≥ 8, respectively (p = 0.001). The actuarial 5-year overall survival (OS) rates were 97.9, 96.4 and 88.6% in the low, intermediate and high-risk groups, respectively, and at the cut-off, the disease-specific survival (DSS) rate of the whole cohort was high (99.1%), as only two high-risk patients died due to PCa. CONCLUSION: Our present results of SBRT delivered with CyberKnife produced excellent long-term bRFS, OS and DSS outcomes among patients with localized PCa. We conclude that SBRT provides an efficient and convenient treatment option for patients with localized PCa, irrespective of the risk-group.

Mitochondrial DNA damage in the hair bulb: can it be used as a noninvasive biomarker of local exposure to low LET ionizing radiation?

Purpose: Our aim was to evaluate whether mitochondrial DNA (mtDNA) damage in hair bulbs could be a suitable biomarker for the detection of local exposure to ionizing radiation.Materials and methods: Mouse hair was collected 4 and 24 hours, 3 and 10 days after single whole-body exposure to 0, 0.1, and 2 Gy radiation. Pubic hair (treated area) and scalp hair (control area) were collected from 13 prostate cancer patients before and after fractioned radiotherapy with an average total dose of 2.7 Gy to follicles after five fractions. Unspecified lesion frequency of mtDNA was analyzed with long PCR, large mtDNA deletion levels were tested with real-time PCR.Results: Unspecified lesion frequency of mtDNA significantly increased in mouse hair 24 hours after irradiation with 2 Gy, but variance among samples was high. No increase in lesion frequency could be detected after 0.1 Gy irradiation. In prostate cancer patients, there was no significant change in either the unspecified lesion frequency or in the proportion of 4934-bp deleted mtDNA in pubic hair after radiotherapy. The proportions of murine 3860-bp common deletion, human 4977-bp common deletion and 7455-bp deleted mtDNA were too low to be analyzed reliably.Conclusions: Our results suggest that the unspecified lesion frequency and proportion of large deletions of mtDNA in hair bulbs are not suitable biomarkers of exposure to ionizing radiation.

A Deep Learning-Based Automated CT Segmentation of Prostate Cancer Anatomy for Radiation Therapy Planning-A Retrospective Multicenter Study.

A commercial deep learning (DL)-based automated segmentation tool (AST) for computed tomography (CT) is evaluated for accuracy and efficiency gain within prostate cancer patients. Thirty patients from six clinics were reviewed with manual- (MC), automated- (AC) and automated and edited (AEC) contouring methods. In the AEC group, created contours (prostate, seminal vesicles, bladder, rectum, femoral heads and penile bulb) were edited, whereas the MC group included empty datasets for MC. In one clinic, lymph node CTV delineations were evaluated for interobserver variability. Compared to MC, the mean time saved using the AST was 12 min for the whole data set (46%) and 12 min for the lymph node CTV (60%), respectively. The delineation consistency between MC and AEC groups according to the Dice similarity coefficient (DSC) improved from 0.78 to 0.94 for the whole data set and from 0.76 to 0.91 for the lymph nodes. The mean DSCs between MC and AC for all six clinics were 0.82 for prostate, 0.72 for seminal vesicles, 0.93 for bladder, 0.84 for rectum, 0.69 for femoral heads and 0.51 for penile bulb. This study proves that using a general DL-based AST for CT images saves time and improves consistency.

Radiation-induced accelerated aging of the brain vasculature in young adult survivors of childhood brain tumors.

BACKGROUND: Cranial radiotherapy may damage the cerebral vasculature. The aim of this study was to understand the prevalence and risk factors of cerebrovascular disease (CVD) and white matter hyperintensities (WMHs) in childhood brain tumors (CBT) survivors treated with radiotherapy. METHODS: Seventy CBT survivors who received radiotherapy were enrolled in a cross-sectional study at a median 20 years after radiotherapy cessation. The prevalence of and risk factors for CVD were investigated using MRI, MRA, and laboratory testing. Tumors, their treatment, and stroke-related data were retrieved from patients' files. RESULTS: Forty-four individuals (63%) had CVD at a median age of 27 years (range, 16-43 years). The prevalence rates at 20 years for CVD, small-vessel disease, and large-vessel disease were 52%, 38%, and 16%, respectively. Ischemic infarcts were diagnosed in 6 survivors, and cerebral hemorrhage in 2. Lacunar infarcts were present in 7, periventricular or deep WMHs in 34 (49%), and mineralizing microangiopathy in 21 (30%) survivors. Multiple pathologies were detected in 44% of the participants, and most lesions were located in a high-dose radiation area. Higher blood pressure was associated with CVD and a presence of WMHs. Higher cholesterol levels increased the risk of ischemic infarcts and WMHs, and lower levels of high-density lipoprotein and higher waist circumference increased the risk of lacunar infarcts. CONCLUSIONS: Treating CBTs with radiotherapy increases the risk of early CVD and WMHs in young adult survivors. These results suggest an urgent need for investigating CVD prevention in CBT patients.

Major reduction of monitor units with the avoidance of leaf-sequencing step by direct aperture based IMRT optimisation.

BACKGROUND AND PURPOSE: Compared with conventional 3D conformal radiotherapy (3D-CRT) the use of intensity-modulated radiation therapy (IMRT) has increased monitor units (MUs) in the delivery of prescribed dose to the patient and thus a potential risk of radiation-induced secondary cancer. Due to the elimination of the leaf-sequencing step in direct aperture based IMRT optimisation (DABO) the MUs in the beam delivery can be reduced. We compared MUs calculated by DABO with other IMRT techniques and 3D-CRT. MATERIAL AND METHODS: Treatment plans for five head and neck cancer patients using dynamic IMRT technique (DMLC) and step-and-shoot (SMLC) technique (Varian Helios Cadplan), 3D-CRT (Varian Eclipse) and a home-made DABO were produced. The total number of MUs, dose coverage and standard deviation of prescribed dose in planning target volume (PTV) between different techniques were compared. RESULTS: In all patients the PTV coverage and sparing of critical structures between the DABO, Helios DMLC and SMLC IMRT techniques was equivalent. Average MUs for beam delivery were 883 MU, 683 MU, 379 MU and 411 MU for DMLC, SMLC, DABO and 3D-CRT, respectively. CONCLUSIONS: The DABO IMRT technique is able to produce treatment plans equivalent in target coverage, dose uniformity and normal tissue sparing compared with the commercial IMRT techniques. The number of MUs with DABO were reduced with a factor of 2.3 (DMLC) and 1.8 (SMLC). The study suggests that with DABO IMRT technique the risk of secondary cancer can be reduced without compromise in the quality of treatment plans.

Critical Appraisal of the Risk of Secondary Cancer Induction From Breast Radiation Therapy With Volumetric Modulated Arc Therapy Relative to 3D Conformal Therapy.

PURPOSE: To evaluate the excess absolute risk (EAR) comparing volumetric modulated arc therapy (VMAT) and 3-dimensional (3D) conformal radiation therapy (CRT) in breast cancer radiation therapy treatment. METHODS AND MATERIALS: Two VMAT arrangements (VMAT_tang and VMAT_full, i.e. partial arcs with and without a sector of 0 Monitor Unit, respectively) and a 3D CRT (field-in-field [FinF]) plan were calculated with an accurate dose calculation algorithm, Acuros, in 20 patients presenting with early-stage breast cancer. The dose prescription was 40.05 Gy in 15 fractions. The planning aim was to maximize the dose reduction in the lungs, contralateral breast, heart, and coronary artery. EAR was estimated using different models: linear, linear-exponential, plateau, and full model, which better uses a carcinogenesis model and epidemiologic data for carcinoma induction and which accounts for cell repopulation or repair during the radiation therapy dose fractionation. EAR was computed for contralateral structures-breast and lung-as well as the ipsilateral lung. Normal tissue complication probability (NTCP) was computed to estimate the ipsilateral lung, heart, and skin toxicity, to balance with respect to second cancer induction. RESULTS: The planning objectives were fulfilled with all the planning techniques. EAR for contralateral breast carcinoma induction, estimated with the most accurate model, was 1.7, 2.4, and 8.5 (per 10,000 patients per year) with FinF, VMAT_tang, and VMAT_full, respectively. For the contralateral lung, these figures were 1.5, 1.6, and 7.3 (per 10,000 patients per year), respectively. NTCP for all the analyzed endpoints was significantly higher with FinF relative to both VMAT settings, with VMAT_full presenting the lowest toxicity risk. CONCLUSIONS: VMAT, in particular with the VMAT_tang setting, could have the same risk of second cancer induction as 3D CRT delivered with the FinF setting for the contralateral organs while reducing acute and late NTCP for the ipsilateral organs. VMAT might be considered a safe technique for breast cancer treatment for those aspects.

Dosimetric evaluation of modern radiation therapy techniques for left breast in deep-inspiration breath-hold.

PURPOSE: The dosimetric differences between four radiation therapy techniques for left sided whole breast irradiation were evaluated side by side in the same patient population. METHODS: Radiotherapy treatment plans were retrospectively created with Accuray TomoDirect (TD), Elekta Volumetric Modulated Arc Therapy (E-VMAT), Varian RapidArc (RA) and Field-in-field (FinF) technique for 20 patients, who had received left breast irradiation during deep-inspiration breath-hold. Dose characteristics of planning target volume and organs at risk were compared. RESULTS: The E-VMAT, TD and RA treatment plans had higher target coverage (V95%) than FinF plans (97.7-98.3% vs. 96.6%). The low-dose spillage to contralateral breast and lung was smaller with FinF and TD (mean 0.1 and 0.3 Gy) compared to E-VMAT and RA (mean 0.6 and 0.9 Gy). E-VMAT, RA and TD techniques were more effective than FinF in sparing left anterior descending artery (mean 4.0, 4.2 and 4.7 Gy vs. 6.1 Gy, respectively). CONCLUSIONS: In whole breast irradiation TD, E-VMAT and RA plans generated in this study achieved higher dose coverage and sparing of organs from the high dose in the vicinity of the PTV. The advantage of calculated FinF plans is the lowest dose on contralateral organs. The choice of the technique used should be weighted by each institution taking into account the dose characteristics of each technique and its fit with patient anatomy bearing in mind the increased workload of using modulated techniques and the increased beam on time.

A photographic technique for quick assessment of mechanical isocenter of a linear accelerator.

Demands for mechanical accuracy of medical linear accelerators are increased due to the stereotactic and modulated rotational treatments. Mechanical inaccuracies affect the size and shape of the mechanical and radiation isocenters. In practice, the mechanical isocenter is defined by the intersection of rotational axes. However, there are no simple tools to check the properties of the mechanical isocenter in 3D. We introduce a new photography-based method for quick and sub-millimeter accurate determination of the mechanical isocenter. The method is based on image-processing algorithm and modified front pointer. The results demonstrate the quick measurement and visualization of the mechanical isocenter.